Palmitic acid modified liposomes as promising nanoplatform for encapsulation of bioactive peptides: Physicochemical, stability, controlled release and intestinal absorption analysis

Despite the growing identification of food-derived bioactive peptides, their health-promoting effects are often hindered by low oral bioavailability. To address this challenge, we hypothesized that structural modification of liposomes with palmitic acid (PA) could enhance gastrointestinal stability and intestinal permeation to improve peptide bioavailability. Here, we successfully prepared the PA modified liposomes through thin-film hydration technique. The results demonstrated that PA was successfully inserted into the liposome membranes, meanwhile increased liposome size (from 139 nm to 146 nm) and enhanced surface charge (from −15 mV to −18 mV). Fourier transform infrared spectroscopy and fluorescence analysis revealed that PA improved the integrity of the phospholipid bilayer through hydrogen bond and electrostatic repulsion, thereby enhancing controlled release profile of liposomes in simulated digestive fluids. Storage stability tests demonstrated that while the liposomes effectively prevented peptide degradation, PA decreased liposome stability at lower temperatures. Importantly, PA-modified liposomes significantly enhanced intestinal permeation efficiency and promoted Caco-2 cellular uptake without inducing cytotoxicity (>90 % cell viability). Overall, the liposomes with PA modification provide an effective nano platform for improving the bioavailability of bioactive peptides